Tay-Sachs, Sandhoff, and LOTS disease is fatal genetic disorder in which harmful quantities of a fatty substance called ganglioside GM2 accumulate due to insufficient activity of an enzyme hexosaminidase. Currently, there is no treatment. Three sub-studies are proposed. Study 1 will focus on the developmental course of the spectrum of infantile Tay-Sachs disease from retrospective data. Study 2 will gather longitudinal prospective data from patients with infantile disease seen at the University of Minnesota to delineate the natural history of Tay-Sachs. Study 3 will be a longitudinal study of LOTS to understand the progression of CNS disease using quantitative methods of neuroimaging and neuropsychological measures. Objectives: Aim 1: Develop an index of disease progression in infantile Tay-Sachs disease through: A. First, a retrospective medical chart/record review for clinical data points. Second, participant caretakers of infants with Tay-Sachs disease will be asked to complete the University of Minnesota Natural History Study Questionnaire for Infantile Tay-Sachs Disease (MNQSTD). B. Prospective: We will collect longitudinal neuropsychological and neuroimaging data in patients with infantile Tay Sachs disease to characterize the developmental course and longitudinally examine individual growth trajectories. Predictors will include mutation type, age at diagnosis, biomarkers and surrogate markers such as MRI results. Aim 2: To better understand the underlying CNS structure and function abnormalities in LOTS disease and to measure change in function over time through neuroimaging and neuropsychological data. Methods: Infantile: Recruit 5 new patients the 1st year, 10 the 2nd year, and 10 the 3rd year. Each child will be seen yearly for a total of at least 3 or possibly 4 follow-up visits within the 5 year period. LOTS: Participants: Recruit 5 new patients the 1st year and 10 new patients the 2nd year. Each patient will be seen once a year. Both Infantile and LOTS: quantitative neuroimaging, biomarkers, and neuropsychological protocol will be used to collect data as well as relevant medical records.